By Donald Zuhn --
Last week, Allele Biotechnology & Pharmaceuticals, Inc. announced that the U.S. Patent and Trademark Office has issued U.S. Patent No. 7,422,896, which is directed to DNA compositions that mediate RNA interference (RNAi) gene silencing, wherein the DNA compositions include an RNA polymerase III promoter that drives the expression of a nucleotide sequence encoding an intermediate small interfering RNA (siRNA) molecule, and RNA polymerase III terminator. The '896 patent is the second U.S. patent to be awarded to Allele Biotech, which is also named as an assignee on U.S. Patent Application Publication No. 2005/0042603.
According to the San Diego-based biotechnology company's press release, the '896 patent supplements a patent that was issued to Allele Biotech last year (U.S. Patent No. 7,294,504) by describing additional ways of using RNA polymerase III and its promoters to express siRNA or shRNA (small or short hairpin DNA) in human and other mammalian systems. The '896 patent covers Allele Biotech's LineSilence and SilenCircle (see below; "Method Overview" from SilenCircle Complete RNAi Kit brochure) platforms, which in contrast to traditional synthetic siRNA platforms, utilize DNA constructs encoding siRNA or shRNA molecules to allow for the induction of RNAi inside target cells. Allele Biotech President and CEO Dr. Jiwu Wang noted that the '896 and '504 patents put the company "in a unique position for co-development in the RNAi research tool and therapeutic fields."
The '896 patent issued from U.S. Application No. 10/217,564, filed August 12, 2002, which is a continuation-in-part of U.S. Application No. 10/202,479, filed July 23, 2002, which issued as the '504 patent, and which claims the benefit of U.S. Provisional Application No. 60/343,697, filed December 27, 2001. Independent claim 1 of the '896 patent recites:
1. A DNA-mediated silencing of gene (DMSG) cassette, comprising, in operative linkage, a distal sequence element (DSE), an RNA polymerase III (pol III) promoter, an expressible template nucleotide sequence, and at least one pol III terminator,
wherein the terminator comprises SEQ ID NO:50,
wherein the DSE is about -79 to -72 nucleotides upstream of the expressible template nucleotide sequence,
wherein the expressible template nucleotide sequence is heterologous with respect to the pol III promoter,
wherein the expressible template nucleotide sequence consists of at least about 16 nucleotides encoding an intermediate small interfering ribonucleic acid (RNA) molecule (siRNA), which mediates RNA interference of a target RNA, said intermediate siRNA comprising:
a) a 5' portion, which comprises at least about 15 nucleotides complementary to a sense strand of the target RNA, and, optionally,
a 3' terminal portion, comprising about 1 to 5 nucleotides,
wherein the intermediate siRNA selectively hybridizes to the sense strand of the target RNA; or
b) a 5' portion, which comprises at least about 15 nucleotides complementary to an antisense strand of the target RNA, and, optionally,
a 3' terminal portion, comprising about 1 to 5 nucleotides,
wherein the intermediate siRNA selectively hybridizes to the antisense strand of the target RNA, and wherein the encoded intermediate siRNA does not activate PKR in a mammalian cell.
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